CircTYW1 serves as a sponge for microRNA-380 in accelerating neurological recovery following spinal cord injury via regulating FGF9

Cell Cycle. 2021 Sep;20(18):1828-1844. doi: 10.1080/15384101.2021.1962634. Epub 2021 Aug 10.

Abstract

As one of the most severe kinds of neurological damage, spinal cord injury (SCI) contributes to persistent motor dysfunction and involves a large repertoire of gene alterations. The participation of circular RNAs (circRNAs) in neurological recovery following SCI needs to be clarified. In the current work, we attempted to assess the function of hsa_circRNA_0003962/circTYW1 and its underlying mechanism in SCI. By accessing the GEO repository, the expression of circTYW1, microRNA-380 (miR-380), and FGF9 in SCI and sham-operated rats was evaluated. PC12 cells after oxygen-glucose deprivation (OGD) treatment were prepared to mimic the SCI model. circTYW1 and FGF9 were poorly expressed, whereas miR-380 was highly expressed in the spinal cord tissues of SCI rats. circTYW1 promoted neurological recovery in SCI rats and inhibited apoptosis in spinal cord tissues. In PC12 cells exposed to OGD, circTYW1 suppressed PC12 cell apoptosis; however, miR-380 overexpression reversed the protective effect of circTYW1 on PC12 cells. Also, circTYW1 promoted FGF9 expression through competitively binding to miR-380, which activated the ERK1/2 signaling. In summary, our results demonstrated that declines in circTYW1 prevented SCI rats from neurological recovery by regulating the miR-380/FGF9/ERK1/2 axis, which might provide new understanding for SCI treatment.

Keywords: Spinal cord injury; erk1/2 signaling; fgf9; hsa_circRNA_0003962/circTYW1; microRNA-380.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Hypoxia / genetics
  • Disease Models, Animal
  • Fibroblast Growth Factor 9 / genetics
  • Fibroblast Growth Factor 9 / metabolism*
  • Glucose / metabolism
  • MAP Kinase Signaling System / genetics*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neurons / metabolism*
  • PC12 Cells
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / genetics*
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / metabolism*
  • Transfection

Substances

  • Fgf9 protein, rat
  • Fibroblast Growth Factor 9
  • MIRN380 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Glucose